Methods, Compositions and Devices For Promoting Anglogenesis

Abstract

This disclosure is, at least in part, directed to compositions, devices, and methods of promote angiogenesis.

Description

RELATED APPLICATIONS[0001]This application claims priority to U.S. Ser. No. 60 / 695,266 filed Jun. 30, 2005 and hereby incorporated by reference in its entirety.INTRODUCTION[0002]Many individuals suffer from circulatory diseases caused by a progressive atherosclerosis that also affects the heart and other major organs. Arterial occlusive diseases and ischemic heart diseases result in 500,000-600,000 deaths in the United States annually.[0003]Vascular stents have now been used clinically for more than a decade to treat peripheral arterial occlusive disease percutaneously. Although the use of stents relieves the initial occlusion of the vessel, the implantation procedure can also damage the fragile endothelium, leading to proliferation of underlying smooth muscle cells and ultimately vascular stenosis caused by neointimal hyperplasia. For example, in percutaneous transluminal coronary angioplasty, the endothelium undergoes virtually complete desquamation at the treatment site due to th...

AI Technical Summary

Benefits of technology

[0003]Vascular stents have now been used clinically for more than a decade to treat peripheral arterial occlusive disease percutaneously. Although the use of stents relieves the initial occlusion of the vessel, the implantation procedure can also damage the fragile endothelium, leading to proliferation of underlying smooth muscle cells and ultimately vascular stenosis caused by neointimal hyperplasia. For example, in percutaneous transluminal coronary angioplasty, the endothelium undergoes virtually complete desquamation at the treatment site due to the luminally-positioned catheter-based instrumentation. Placement of metallic stents, which are used in roughly 80-90% of procedures currently, has helped reduce, but not eliminate, restenosis caused by the damage to the interior wall of vessels during angioplasty; whereas chronic constrictive vessel remodeling occurs after balloon angioplasty alone, placement of a metal stent scaffold eliminates this chronic recoil of the vessel.

[0004]In addition, the stent material itself is foreign and provides sites for protein adsorption which can lead to platelet activation and thrombus formation, exacerbating the risk of thrombosis incited by endothelial removal. This risk is typically mitigated by administering platelet inhibitors systemically during the first month following the procedure. As a result, systemic anticoagulation regimens (e.g., use of heparin for short term applications; low molecular weight heparinoids, Plavix, and other anti-platelet agents for longer term) are almost always required clinically to reduce the risk of thrombus formation. The long-term use of exogenous anticoagulants, however, can also have adverse effects, especially a greatly increased possibility of hemorrhage. In addition, even when anticoagulant levels can be managed effectively, thrombocytopenia (platelet consumption) and thrombosis can still occur. Further, there is always risk of bleeding when patients are on given anticoagulants.

Problems solved by technology

Although the use of stents relieves the initial occlusion of the vessel, the implantation procedure can also damage the fragile endothelium, leading to proliferation of underlying smooth muscle cells and ultimately vascular stenosis caused by neointimal hyperplasia.

In addition, the stent material itself is foreign and provides sites for protein adsorption which can lead to platelet activation and thrombus formation, exacerbating the risk of thrombosis incited by endothelial removal.

The long-term use of exogenous anticoagulants, however, can also have adverse effects, especially a greatly increased possibility of hemorrhage.

In addition, even when anticoagulant levels can be managed effectively, thrombocytopenia (platelet consumption) and thrombosis can still occur.

Further, there is always risk of bleeding when patients are on given anticoagulants.

No such agents have been found to date that promote angiogenesis.

Thus, although nitric oxide agents have been shown to mitigate restenosis, nitric oxide has not been shown to be of therapeutic benefit in promoting, or enhancing endothelial repair at sites of vascular injury.

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